Several publications and patent documents are cited throughout the specification in order to describe the state of the art to which this invention pertains. Each of these citations is incorporated herein by reference as though set forth in full.
Ferroportin (ferroportin 1, also termed Ireg1, MTP1, SLC40A1) is a cell surface transmembrane protein and is the only known export protein for non-heme iron (1-3). Ferroportin is expressed at high levels on duodenal enterocytes, placenta, hepatocytes, and macrophages (1-3), and is an essential component of systemic iron homeostasis (4). Ferroportin is regulated by at least three mechanisms: transcriptional regulation, which controls levels (5) and splice variants (6) of the mRNA; translational regulation, which regulates ferroportin through an iron regulatory element in the 5′ UTR of ferroportin mRNA (7); and organismal iron status, which regulates ferroportin mediated iron efflux through a direct interaction of ferroportin with the peptide hormone hepcidin (8). Hepcidin is secreted by the liver and binds to a specific extracellular loop domain on ferroportin (9). This results in phosphorylation (10) of ferroportin on the cell surface, which in turn leads to internalization and proteosome-mediated degradation of ferroportin (8).
Ferroportin has not been extensively studied in cancer (11, 12), and only limited examination has been made of ferroportin outside the tissues generally thought to be important in systemic iron homeostasis, such as the intestine, the liver, the bone marrow, and the reticulo-endothelial system (13).